What is Obliterative bronchiolitis (OB)

Obliterative bronchiolitis, also known as bronchiolitis obliterans, is a manifestation of chronic allograft rejection, that is, rejection following organ transplantation from another human being. It develops in nearly 50 percent of all patients who receive a lung transplant from an unrelated donor.
Obliterative bronchiolitis is a severe inflammatory response provoked by lung transplantation from an unrelated donor. The inflammatory response causes a large number of lymphocytes (a type of white blood cell that fights infection) to come into the graft tissue (transplanted tissue), resulting in fibrosis (increase in fibrous tissue) and progressive narrowing of the airway. This can cause airway obstruction and is a major cause of death in patients after receiving lung transplantation.

Statistics on Obliterative bronchiolitis (OB)

OB is the major obstacle to prolonged survival following lung transplatation. Survival following lung transplantation is significantly poorer as compared to transplatation of other organs.
Although obliterative bronciolitis is rare within the first year after transplantation, it becomes common beyond the first year. It happens to a total of 50 to 80% of patients in a period of 5 years following lung tranplantation.

Risk Factors for Obliterative bronchiolitis (OB)

Patients with acute allograft rejection (rejection to the foreign organ shortly after tranplantation), especially those with multiple or severe episodes, are at a significantly increased risk of developing obliterative bronchiolitis.
Other risk factors include mismatching of HLA (the major histocompatibility complex in humans), pneumonia caused by a virus called cytomegalovirus and injury to the airways or transplanted tissue.
A new study shows that exposure to a chemical called diacetyl, a component of artificial butter flavouring, can be harmful to the nose and airways of mice. Scientists at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health, conducted the study because diacetyl has been implicated in causing obliterative bronchiolitis in humans. Obliterative bronchiolitis has been detected recently in workers who inhale significant concentrations of the flavouring in microwave popcorn packaging plants. When laboratory mice inhaled diacetyl vapors for three months, they developed lymphocytic bronchiolitis – a potential precursor of obliterative bronchiolitis . None of the mice, however, were diagnosed with obliterative bronchiolitis.

Progression of Obliterative bronchiolitis (OB)

The time frame from lung transplantation to the start of symptoms of obliterative bronchiolitis is variable, ranging from 3 months to more than 9 years after transplantation.
Once obliterative bronchiolitis develops, the lung function typically declines progressively. Generally, progressive obstruction to airflow results in exercise limitation, repetitive lung infections, and, eventually, death due to poor lung function.
The course of BOS, however, varies between individuals. Some patients experience rapid loss of lung function and die in a few months. Others progress slowly, followed by prolonged stability.
Obliterative bronchiolitis has been graded into 5 categories based on the FEV1, which is the volume of air that can be forced out in one second after taking a deep breath.
The five categories are BOS 0, BOS 0p, BOS 1, BOS 2, and BOS 3, with declining lung function as the grade goes higher.

How is Obliterative bronchiolitis (OB) Diagnosed?

The doctor will perform a lung function test measuring the FEV1, which is the volume of air that can be forced out in one second after taking a deep breath.
Some other tests like bronchoalveolar lavage (lung washings) and culture may be carried out in some centres.

Prognosis of Obliterative bronchiolitis (OB)

The death rate at 3 years after the start of obliterative bronchiolitis is more than 50%.
The survival rate at 5 years after the start of the disease is only 30 to 50%.
Patients who develop obliterative bronchiolitis within the first 3 years after transplatation have a poorer outcome. A majority of these patients have a greater decline in lung function, greater need for oxygen and a higher rate of transplant failure (requiring retransplantation) or death.

How is Obliterative bronchiolitis (OB) Treated?

    • Treat specific complications
    • Treat/prevent episode of acute rejection (rejection shortly after transplantation)
    • Oxygen supplement
    • Drugs to dilate (widen) the airways to relieve symptoms from airway obstruction

 
Some other treatment options may be considered:

  • Increased immunosuppression (to suppress the inflammatory response)
  • Drugs like tacrolimus, mycophenolate mofetil (MMF), cytolytic therapy

A second transplantation of the lung may be considered in some cases, if possible.
A recent study demonstrated in experimental mice that inhalation of safe and controlled doses of carbon monoxide for several weeks after transplant surgery prevented the development of obliterative bronchiolitis. This might be a useful treatment option in the future but further research is still needed. Since carbon monoxide is a poisonous gas, care must be taken in terms of dosage in any future therapy to prevent toxicity.

Obliterative bronchiolitis (OB) References

  1. Hertz MI, Taylor DO, Trulock EP, et al. The registry of the international society for heart and lung transplantation: nineteenth official report-2002. J Heart Lung Transplant 2002; 21: 950-70.
  2. Heng D, Sharples LD, McNeil K, et al. Bronchiolitis obliterans syndrome: incidence, natural history, prognosis, and risk factors. J Heart Lung Transplant 1998; 17: 1255-63.
  3. Estenne M, Maurer JR, Boehler A, et al. Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria. J Heart Lung Transplant 2002; 21: 297-310.
  4. Brugiere O, Pessione F, Thabut G, et al. Bronchiolitis obliterans syndrome after single-lung transplantation: impact of time to onset on functional pattern and survival. Chest 2002; 121: 1883-9.
  5. Belperio JA, Lake K, Tazelaar H, Keane MP, Strieter RM, Lynch JP. Bronchiolitis obliterans syndrome complicating lung or heart-lung transplantation. Semin Respir Crit Care Med 2003; 24(5): 499-530.
  6. Estenne M, Hertz MI. Bronchiolitis obliterans after human lung transplantation. Am J Respir Crit Care Med 2002; 166: 440-4.
  7. Minamoto K, Harada H, Lama VN, Fedarau MA, Pinsky DJ. Reciprocal regulation of airway rejection by the inducible gas-forming enzymes heme oxygenase and nitric oxide synthase. J Exp Med 2005; 202: 283-94.
  8. Morgan DL, Flake GP, Kirby PJ, Palmer, SM. Respiratory toxicity of diacetyl in C57Bl/6 mice. Toxicological Sciences. Advance Access published on January 27, 2008.